We have investigated the disposition of suramin in the isolated perfused rat liver preparation (IPRL) after the administration of suramin (18 mg, 8 muCi). At 30 min post drug administration, almost 100% of the [14C]radioactivity and unchanged suramin were located in the perfusate plasma. During the course of the study, the elimination of suramin from the IPRL was barely perceptible. The AUC0-5 hr of suramin (730.6 +/- 86.2 micrograms hr/ml) corresponded to that of [14C] radioactivity (815.1 +/- 105.5 micrograms ml/hr) at 5 hr, indicating a lack of perfusate suramin metabolites. At 5 hr only a small proportion of [14C] radioactivity was recovered from the livers (2.5 +/- 1.1%). Subsequent HPLC analysis of the liver tissue indicated this to be unchanged suramin. Sub-cellular fractionation of the homogenised livers revealed suramin to be distributed in the liposomal rich tissue fractions (10,000 g pellet, 1.6 +/- 0.8%; 105,000 g supernatant, 1.1 +/- 0.35%). Biliary excretion of [14C] radioactivity was low (2.1 +/- 0.7%), however, none could be accounted for as unchanged suramin. Previously undetected metabolites of suramin may have accounted for the unidentified biliary radioactivity.